Protective effects of scutellarin in experimental colitis in rats.

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology for which effective treatments are lacking. Scutellarin is a flavonoid with anti-apoptotic, antioxidant and anti-inflammatory effects. We investigated the possible protective effects of scutellarin on UC induced by acetic acid in rats. We used five groups of male rats: control, scutellarin, UC, UC + scutellarin, UC + sulfasalazine. Colonic mucosal inflammation was evaluated microscopically. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and DNA fragmentation levels were measured. Colon tissue sections were evaluated using immunohistochemistry for Bcl-2 and Bax, TUNEL staining and histopathology. Pretreatment with scutellarin significantly reduced histological damage. Scutellarin significantly reduced serum and tissue levels of MDA, NO, IL-6 and TNF-α, and increased enzymatic activity of SOD and TAS. Scutellarin suppressed apoptosis by down-regulation of Bax, reduction of DNA fragmentation and increased expression of Bcl-2. Apoptosis was increased, while antioxidant enzymes were significantly decreased; some histopathologic disorders also were seen in the UC group. Administration of scutellarin ameliorated the pathological and biochemical alterations caused by UC in rats. We found that scutellarin might be protective against UC by down-regulating pro-inflammatory cytokines and suppressing apoptosis and oxidative stress.

Does protocatechuic acid, a natural antioxidant, reduce renal ischemia reperfusion injury in rats?

BACKGROUND: Protocatechuic acid (PCA), which has antioxidant property, is a simple phenolic compound commonly found in many plants, vegetables, and fruits, notably in green tea and almonds. Present study was an investigation of the effects of PCA on rat kidney with ischemia/reperfusion (IR) injury. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: (1) Sham, (2) Renal IR, (3) Renal IR+Vehicle, and (4) Renal IR+PCA. Renal reperfusion injury was induced by clamping renal pedicle for 45 minutes after right nephrectomy was performed, followed by reperfusion for 3 hours. Dose of 80 mg/kg PCA was intraperitoneally administered to 1 group immediately before renal ischemia; 33% polyethylene glycol was used as vehicle. Total antioxidant status (TAS), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), and interleukin-6 levels were measured in blood and kidney tissue samples taken from sacrificed rats. Kidney tissue samples were examined and scored histopathologically. Terminal deoxynucleotidyltransferase-mediated dUTP digoxigenin nick end labeling assay method was used to detect apoptotic cells. RESULTS: It was found that PCA significantly reduced serum MDA, TNF-α, and kidney MDA levels, while it increased serum and kidney TAS and SOD levels. Histopathological scores were significantly higher for the group given PCA. CONCLUSION: PCA reduced oxidative stress and can be used as an effective agent in treatment of renal IR injury.

The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.

Cabazitaxel causes a dose-dependent central nervous system toxicity in rats.

BACKGROUND: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. AIM: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system. METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5mg/kg), group 3 (Cabazitaxel 1.0mg/kg) and group 4 (Cabazitaxel 1.5mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. RESULTS: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner. CONCLUSION: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.

The Syk Inhibitor Fostamatinib Decreases the Severity of Colonic Mucosal Damage in a Rodent Model of Colitis.

BACKGROUND AND AIMS: Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal system. In some cases, current medications used for inflammatory bowel disease may not be enough for remission, creating a need for more potent and reliable medications. There is no study showing the efficacy of fostamatinib, with proven effects on some inflammatory diseases, on ulcerative colitis. In our study we planned to research the efficacy of fostamatinib, a spleen tyrosine kinase inhibitor, on acetic acid-induced colitis. METHODS: The study included 28 male Sprague-Dawley rats, randomly divided into control group, fostamatinib group, colitis group and fostamatinib + colitis group, each containing seven rats. Colitis induction was performed with 4% acetic acid. Colonic inflammation was assessed with disease activity index, macroscopic and histological damage scores, colonic myeloperoxidase, malondialdehyde and superoxide dismutase activity, and tumour necrosis factor alpha [TNFα], CD3, Syk, and phospho-Syk expression. RESULTS: There was a significant difference between the colitis and control groups in terms of all parameters. The disease activity index, macroscopic and microscopic damage scores, immunohistochemical TNFα, CD3, Syk, and phospho-Syk expression, and tissue myeloperoxidase activity were found to be significantly lower in the colitis + fostamatinib group compared with the colitis group. There was no significant difference between the two groups in terms of myeloperoxidase and malondialdehyde activity. CONCLUSIONS: Fostamatinib reduced the inflammatory damage in the experimental colitis. This effect may be due to suppression of TNFα, T-lymphocytes, and neutrophils in colonic mucosa via suppression of Syk. Fostamatinib may be an appropriate treatment alternative for ulcerative colitis. Further clinical studies are required to support this.

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

BACKGROUND: To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats. METHODS: Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA. RESULTS: The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

Determination of DNA damage in experimental liver intoxication and role of N-acetyl cysteine.

The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl4 intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl4 in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl4 injection and continued during the experimental period. Control groups were given olive oil and N-acetyl cysteine. After 6 and 72 h of CCl4 injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl4 caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl4 intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl4-induced DNA damage.

The protective effect of selenium in cisplatin-related retinotoxicity.

PURPOSE: The aim of this study is to evaluate the retinal toxicity of cisplatin and neuroprotective effect of selenium in cisplatin-related retinal toxicity. METHODS: Eighteen adult Wistar-Albino rats were divided into three groups. Group 1 (n = 6) received intraperitoneal (i.p.) injection of 2.5 ml physiologic saline for three days, group 2 (n = 6) received i.p. 16 mg/kg cisplatin for three days and group 3 (n = 6) received i.p. 16 mg/kg cisplatin for three days and 1.5 mg/kg twice daily selenium via gavage five days prior to cisplatin injection and for three days concomitantly with cisplatin injections. The total retinal thickness, outer nuclear layer (ONL), inner nuclear layer (INL) and inner plexiform layer (IPL) thicknesses were measured in hematoxylin/eosin and apoptotic index (AI) of ganglion cell layer (GCL) and INL was evaluated in TdT-mediated dUTP-biotin nick end labeling (TUNEL)-stained retina sections. RESULTS: Selenium statistically succeeded to reduce total retinal thickness in cisplatin-toxicated retinas: from 210.17 ± 23.40 to 173.55 ± 20.43, ONL: 49.79 ± 5.32 to 41.87 ± 6.30, INL: 33.72 ± 7.93 to 25.06 ± 5.73 and IPL: 53.61 ± 8.63 to 45.61 ± 6.92 µm in hematoxylin/eosin-stained retina sections. The AI was also reduced in INL (30.10 ± 12.02 to 19.48 ± 12.99) and in GCL (37.59 ± 17.70 to 33.15 ± 13.78). However, statistical significance was present in only AI values of INL. CONCLUSIONS: Selenium limited edema due to the toxicity and reduced the retinal thickness and showed neuroprotection in cisplatin-induced retinotoxicity.

Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney.

BACKGROUND: To investigate the protective effect of 2-aminoethyl diphenylborinate (2-APB) against ischemia-reperfusion (I/R) injury in the rat kidney by an experimental study. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly divided into the following three groups: (1) sham group, (2) I/R group, and (3) I/R + 2-APB group. Renal I/R injury was induced by clamping the left renal pedicle for 45 min after right nephrectomy, followed by 3 h of reperfusion. The therapeutic agent 2-APB was administered intravenously at a dose of 2 mg/kg 10 min before renal ischemia. Glutathione, superoxide dismutase, total antioxidant capacity, malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were measured from blood samples, and the rats were sacrificed subsequently. Tissue samples were scored histopathologically. Visualization of apoptotic cells was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling staining method. RESULTS: 2-APB significantly reduced serum malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels in the I/R injury group. However, glutathione, superoxide dismutase, and total antioxidant capacity levels increased significantly. Histopathologic scores were significantly better and the rate of apoptosis was lower in the 2-APB group. CONCLUSIONS: 2-APB reduces oxidative stress and damage caused by renal I/R injury. The results of this study demonstrate that 2-APB can be used as an effective agent against I/R injury in the kidney.

Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis.

OBJECTIVE: The aim was to study the effects of boric acid (BA) and 2-aminoethoxydiphenyl borate (2-APB) on oxidative stress and inflammation in an experimental necrotizing enterocolitis (NEC) rat model. METHODS: Experimental NEC was induced in 40 newborn Sprague-Dawley rats by asphyxia and hypothermia applied in 3 consecutive days. Rats were subdivided into 4 subgroups as NEC, NEC+BA, NEC+2-APB, and controls. BA and 2-APB were applied daily before the procedure. Serum total antioxidant status, superoxide dismutase (SOD), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and erythrocyte glutathione (GSH) levels were measured. Pathological changes for NEC in intestinal architecture were evaluated by a grading system. RESULTS: Pretreatment with BA and 2-APB resulted in a decrease in NEC incidence. In all of the NEC groups, decreased serum levels of GSH and SOD were measured. Boron limited GSH consumption but had no effect on SOD levels. Total antioxidant status levels were not statistically different among groups. In our experimental NEC model, BA, but not 2-APB, prevented the increase of TNF-α. Pretreatment with BA and 2-APB downregulated the activity levels of IL-6 in NEC. CONCLUSIONS: In the experimental NEC model, BA and 2-APB partly prevent NEC formation, modulate the oxidative stress parameters, bring a significant decrease in GSH consumption, and enhance the antioxidant defense mechanism, but have no effect on total antioxidant status. BA inhibits the hypoxia and hypothermia-induced increase in both IL-6 and TNF-a, but 2-APB only in IL-6. Boron may be beneficial in preventing NEC.